ABSTRACT
Magnitude of SARS-CoV-2 virus exposure may contribute to symptom severity. In a sample of seropositive adults (n=1101), we found that individuals who lived with a known COVID-19 case exhibited greater symptom severity and IgG concentrations compared to individuals who were seropositive but did not live with a known case (P<0.0001).
ABSTRACT
BackgroundThe majority of COVID-19 cases are asymptomatic, or minimally symptomatic with management in the home. Little is known about the frequency of specific symptoms in the general population, and how symptoms predict the magnitude of antibody response to SARS-CoV-2 infection. MethodsWe quantified IgG antibodies against the SARS-CoV-2 receptor binding domain (RBD) in home-collected dried blood spot samples from 3,365 adults participating in a community-based seroprevalence study in the city of Chicago, USA, collected between June 24 and November 11, 2020. Results17.8% of the sample was seropositive for SARS-CoV-2. A cluster of symptoms (loss of sense of smell or taste, fever, shortness of breath, muscle or body aches, cough, fatigue, diarrhea, headache) was associated with stronger anti-RBD IgG responses among the seropositives. 39.2% of infections were asymptomatic, and 2 or fewer symptoms were reported for 66.7% of infections. Total number of symptoms was positively but weakly associated with IgG response: Median anti-RBD IgG was 0.95 ug/mL for individuals with 3 or more symptoms, in comparison with 0.61 ug/mL for asymptomatic infections. ConclusionWe document high rates of asymptomatic and mild infection in a large community-based cohort, and relatively low levels of anti-SARS-CoV-2 IgG antibody in the general population of previously exposed individuals.
ABSTRACT
ObjectiveSerological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). MethodsAn ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members. ResultsAmong 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain. ConclusionDBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARSCoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection.
ABSTRACT
BackgroundSerological testing for SARS-CoV-2 IgG antibodies is needed to document the community prevalence and distribution of the virus, particularly since many individuals have mild symptoms and cannot access molecular diagnostic testing of naso-pharyngeal swabs. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of capillary whole blood, collected from a simple finger prick and dried on filter paper (dried blood spot, DBS). MethodsEnzyme linked immunosorbent assay (ELISA) was optimized to detect SARS-CoV-2 IgG antibodies against the receptor-binding domain (RBD) of the spike protein. DBS samples were eluted overnight and transferred to a 96-well plate coated with antigen, and anti-human IgG-HRP was used to generate signal in proportion to bound antibody. DBS samples spiked with anti-SARS IgG antibody, and samples from known positive and negative cases, were compared to evaluate assay performance. ResultsAnalysis of samples with known concentrations of anti-SARS IgG produced the expected pattern of dose-response. Optical density (OD) values were significantly elevated for known positive cases in comparison with samples from unexposed individuals. DiscussionDBS ELISA provides a minimally-invasive alternative to venous blood collection that combines the convenience of sample collection in the home or non-clinical setting with the quantitation of ELISA in the lab. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples should facilitate research across a wide range of community- and population-based settings on seroprevalence, predictors and duration of antibody responses, as well as correlates of protection from reinfection, each of which is critically important for pandemic control.
